Fluid flow stimulates the hair bundles (HB) of the inner hair cells (IHC) of the cochlea opening the mechano-electric transducer (MET) channels of the IHCs. The resulting current depolarizes the cell body inducing neurotransmitter release and, ultimately, auditory nerve stimulation. The active machinery of the cochlea, driven by motility of outer hair cells (OHC), both tunes the microfluidic excitation of the IHC HBs and provides for nonlinear compression. However, the relative influence of OHC somatic and HB motility on this final fluidic forcing in the cochlea has yet to be conclusively apportioned nor has the microfluidi flow that excites the IHC HB. The specific aims of this grant are to develop models of IHC HB stimulation by developing a microfluidic representation of the flow in the subtectorial space and coupling these models to the macroscopic model of the cochlea. In specific aim 2 we seek to determine the tonotopic dependence and combined effect of active OHC forces on the organ of Corti and of the fluidic forces on the IHC HB. The overarching goal of this research is to develop a complete fluid-mechanical-electrical model that describes the response of the cochlea to both external acoustic and internal electrical stimulation. If successful, this model will enhance our understanding of failure mechanisms in the cochlea, answering important questions as to the morphological elements of the cochlea that fail and why. This will improve noninvasive diagnosis of hearing as abnormalities in the response measures can be linked to specific pathologies. Further, as our model can predict the interaction of electrical and acoustic stimulus it will enable a prediction of the effect of a combined acoustic-electric prosthesis (such as would be used in schemes where some residual hearing is still present). Finally, a mathematical model of the cochlear response to sound over the entire spectrum will help us to understand how important classes of signals are processed in the cochlea (such as speech and music) which can lead to better speech processing algorithms or cochlear implant electrical stimulation paradigms. PUBLIC HEALTH RELEVANCE: We seek to understand the active processes that are responsible for normal hearing by building mathematical models simulating the behavior of the cochlea, the transducer of the hearing system. By understanding the cochlea well enough to model it, we hope to predict how the cochlea might fail, say in response to loud sound or age, and guide the development of protective approaches or enhanced prosthetics. In addition, a predictive mathematical model will enable the development of new noninvasive tests to better interrogate the health of one's hearing.